Environmental Factor, July 2007, National Institute of Environmental Health Sciences

NIEHS Spearheads Epigenetics Roadmap Initiative

By Eddy BallJuly 2007

"We'll play a major role in rolling this initiative out," Schwartz
explained. "This is a very exciting development for the
Institute."
(Photo courtesy of Steve McCaw)

Senior Science Advisor Brenda Weis. Schwartz
said of the NIEHS representatives on the
Working Group, "This program would not have
happened had it not been for the dedication of
Brenda and her staff and associates [Heindel
and Tyson]."
(Photo courtesy of Steve McCaw)

On May 30, NIEHS Director David A. Schwartz, M.D., announced that NIH had selected as part of its Roadmap the Epigenetics Initiative prepared by NIEHS in partnership with the National Institute on Drug Abuse (NIDA). Schwartz summarized this project during his report to the National Advisory Environmental Health Sciences Council during its spring meeting in Rodbell Auditorium. The Initiative marks the first time that NIEHS has played such an important role in shaping the NIH Roadmap.

Senior Science Advisor Brenda Weis, Ph.D., gave the council an overview of the trans-NIH initiative. "In typical Roadmap fashion," she said, "we assembled and led a trans-NIH Working Group.... The charge to the group was to develop a compelling research program that would transform biomedical research in the next ten years." What emerged is a comprehensive proposal for realizing coordination, standardization, integration and leadership in the field of epigenetics to facilitate translation of research into clinical applications.

The funding for the Initiative will span a ten year period from fiscal year (FY) 2008 through FY 2017 and could involve between $129.5 and $248.5 million in grants, depending on which version of the program proposal is approved by the NIH Office of Portfolio Analysis and Strategic Initiatives (OPASI). The program includes Roadmap co-funding of up to 15 Institute and Center (IC)-based programs over the ten year period and a $4 million "jump start" allocation in FY 2007.

Following a review of proposals by the 27 NIH IC directors on May 18, the Epigenetics Program, along with a Microbiome Program, was approved for Roadmap 1.5 support. Funding for the Epigenetics Initiative and the Microbiome Initiative (see text box) will come from what is known as the Common Fund, a repository to which each IC contributes annually.

Being a part of the NIH Roadmap recognizes a research area as one of "the most pressing problems facing medical research today that can be uniquely addressed by the NIH as a whole." While funding for a Roadmap initiative will not affect an individual institute's budget beyond its contribution to the Common Fund, the Roadmap itself is subject to the same budget pressures as the rest of the NIH.

As Weis observed in her presentation, epigenetics is an emerging science with nearly 5,000 studies related to epigenetics and its connection to disease published in 2006. The term refers to potentially heritable traits that occur as early as in utero and are not dependent on DNA sequence. These traits have been strongly implicated in cancer and tumor formation and linked to a variety of other conditions, ranging from obesity and diabetes to impairments in memory and learning.

According to Weis, although interest the role of epigenetics in cancer has surged in recent years, research in the field suffers from infrastructure weaknesses, lack of organization and thus far limited focus. The Roadmap 1.5 Epigenetics Initiative, Weis explained, is designed to help this emerging area of science by pursuing four enabling objectives to expand disease-focused research:

Establishing an NIH-led international consortium as part of the $4 million "jump start" allocation

Creating references for the field by developing "maps" for 24 epigenomes in human embryonic stem cells, differentiating and differentiated cells, cell lines and tissue (5 year)

Building a publicly accessible epigenetic database through collaboration with the National Library of Medicine's National Center for Biotechnology Information to develop a computational infrastructure (2 year) integrated with existing public data sources (10 year)

Developing and enhancing technology to identify standard protocols, technology platforms, and reagents for maintenance of stem cells/tissues and epigenetics, including antibodies (10 year)

The Microbiome Initiative

The Microbiome refers to the full collection of microbes (bacteria, fungi, viruses, etc.) that naturally exist within the human body. According to the authors of "Extending Our View of Self: the Human Gut Microbiome Initiative (HGMI)," the adult body typically harbors ~10 times more microbial than human cells, and the distal gut by itself contains up to 100 trillion bacterial cells. Scientists in the field speculate that the human genome could be seen as an amalgam of human genes and the genes of our microbial 'selves.' "Without understanding the interactions between our human and microbial genomes," the authors argue, "it is impossible to obtain a complete picture of human biology."

Initiatives in this area would focus on developing a deeper understanding of these communities of microbes in order to determine how they affect human health. The Roadmap 1.5 Initiative is being led by National Institute of Allergy and Infectious Diseases Director Anthony Faucci, M.D., and Human Genome Research Institute (HGRI) Director Francis Collins, M.D., Ph.D.

While NIEHS was not instrumental in this initiative, the Institute collaborated with HGRI in a special presentation on the Human Microbiome Project at the annual meeting of the American Society for Microbiology in Toronto on May 24. "Our [institute's] interest in the Microbiome is in the toxins released by these microorganisms," Schwartz observed. "The question [for NIEHS] is 'How do we hook into that initiative in a meaningful way?'"

Three additional initiatives, Inflammation, Phenotyping and Protein Capture, were not approved during the first round, but they may be approved later as scaled-down versions.

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